Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs

ABSTRACT

Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs–induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

KEYWORDS:

• Antiepileptic drugs
• bone metabolism
• bone mineral density
• bone turnover markers
• osteoporosis

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Antiepileptic drugs (AEDs) are known to result in various ranges of pathological bone abnormalities including low bone mineral density, osteopenia, osteoporosis, osteomalacia, rickets and fractures.

• Both enzyme-inducing and non-enzyme inducing, old and new AEDs can induce bone diseases.

• Type, dose and duration of treatment and polytherapy are predictors of AEDs-induced bone diseases.

• AEDs may induce vitamin D deficiency or insufficiency, resulting in hypocalcemia, low bone mineral density and secondary hyperparathyroidism. Also, they may directly accelerate bone loss or reduce bone accrual irrespective of vitamin D levels.

• Physicians should counsel and monitor patients taking AEDs for bone health.

• Prophylaxis doses of calcium and vitamin D or institution of appropriate treatment doses with calcium, vitamin D and even antiresorptive drugs are recommended in patients with bone diseases induced by AEDs.